Is DHDDS p.Ile70Leu (c.208A>C) pathogenic?

DHDDS p.Ile70Leu (c.208A>C) is classified Uncertain significance in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-04). AlphaMissense: ambiguous (0.4822); Very rare (popmax 8.47e-05%, nfe); Associated with retinitis pigmentosa 59.

What condition is associated with DHDDS p.Ile70Leu (c.208A>C)?

DHDDS p.Ile70Leu (c.208A>C) is associated with retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Ile70Leu (c.208A>C) in the general population?

DHDDS p.Ile70Leu (c.208A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DHDDS p.Ile70Leu (c.208A>C)?

AlphaMissense predicts ambiguous (score 0.4822) — an in-silico prediction, not a clinical call.

DHDDS p.Ile70Leu

c.208A>C · rs1253678123 · VCV1372483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4822 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

retinitis pigmentosa 59

Computational evidence

Protein change
AlphaMissense	0.4822	ambiguous
REVEL	0.486	indeterminate
SaProt	LLR -10.59	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.81, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 9,886 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,020 alleles

Overall 6.84e-05% 1/1,461,878 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DHDDS
Protein: p.Ile70Leu
Coding: c.208A>C
MANE Select: NM_205861
dbSNP: rs1253678123
Type: single nucleotide variant
Location: chr1:26442758 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 70: a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation)

Full DHDDS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 59 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHDDS p.Ile70= Likely benign ★★ same residue
DHDDS p.Ile70Val Uncertain significance ★ ⚠ same residue
DHDDS c.658-2A>G Likely pathogenic ★★ same condition
DHDDS p.Arg205Gln Pathogenic ★★ same condition
DHDDS p.Arg211Gln Pathogenic ★★ same condition
DHDDS p.Arg37Cys Pathogenic ★★ same condition
DHDDS p.Arg37His Pathogenic/Likely pathogenic ★★ same condition
DHDDS p.Arg37Ser Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dhdds-p-ile70leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown